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Figure S5 from Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

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posted on 2023-03-31, 13:48 authored by Stacey J. Winham, Ailith Pirie, Yian Ann Chen, Melissa C. Larson, Zachary C. Fogarty, Madalene A. Earp, Hoda Anton-Culver, Elisa V. Bandera, Daniel Cramer, Jennifer A. Doherty, Marc T. Goodman, Jacek Gronwald, Beth Y. Karlan, Susanne K. Kjaer, Douglas A. Levine, Usha Menon, Roberta B. Ness, Celeste L. Pearce, Tanja Pejovic, Mary Anne Rossing, Nicolas Wentzensen, Yukie T. Bean, Maria Bisogna, Louise A. Brinton, Michael E. Carney, Julie M. Cunningham, Cezary Cybulski, Anna deFazio, Ed M. Dicks, Robert P. Edwards, Simon A. Gayther, Aleksandra Gentry-Maharaj, Martin Gore, Edwin S. Iversen, Allan Jensen, Sharon E. Johnatty, Jenny Lester, Hui-Yi Lin, Jolanta Lissowska, Jan Lubinski, Janusz Menkiszak, Francesmary Modugno, Kirsten B. Moysich, Irene Orlow, Malcolm C. Pike, Susan J. Ramus, Honglin Song, Kathryn L. Terry, Pamela J. Thompson, Jonathan P. Tyrer, David J. van den Berg, Robert A. Vierkant, Allison F. Vitonis, Christine Walsh, Lynne R. Wilkens, Anna H. Wu, Hannah Yang, Argyrios Ziogas, Andrew Berchuck, Joellen M. Schildkraut, Jennifer Permuth-Wey, Catherine M. Phelan, Paul D.P. Pharoah, Brooke L. Fridley, Thomas A. Sellers, Ellen L. Goode

Supplemental Figure S 5

Funding

NIH Office of Research on Women's Health

Genetic Associations and Mechanisms in Oncology (GAME-ON), an NCI Cancer Post-GWAS Initiative

NHMRC

University of Sydney Cancer Research Fund and the Cancer Institute NSW through the Sydney West Translational Cancer Research Centre

NIH

Medical Research Council Studentship

Eve Appeal and the Oak Foundation

AUS: U.S. Army Medical Research and Materiel Command

National Health & Medical Research Council of Australia

Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania, Cancer Foundation of Western Australia. DOV

HAW: NIH

HOP: US Army Medical Research and Material Command

NCI

NIH/National Center for Research Resources/General Clinical Research Center

LAX: American Cancer Society Early Detection Professorship

National Center for Advancing Translational Sciences (NCATS)

United States Department of Health and Human Services

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NCI, Bethesda, MD

Danish Cancer Society, Copenhagen, Denmark

Mermaid I project

MAC and MAY: NIH

NCO: Department of Defense

NEC: NIH

Department of Defense

NJO: NCI

Cancer Institute of New Jersey

ORE: OHSU Foundation

POC: Pomeranian Medical University

RMH: Cancer Research UK, Royal Marsden Hospital

SEA: Cancer Research UK

UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, SEARCH team, Craig Luccarini, Caroline Baynes, Don Conroy; UKO: The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

USC

California Cancer Research Program

History

ARTICLE ABSTRACT

Background: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC).Methods: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped).Results: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E−6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E−6; Pcorrected = 0.01).Conclusions: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed.Impact: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study. Cancer Epidemiol Biomarkers Prev; 25(3); 446–54. ©2016 AACR.

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